Effect of exercise on reactivity and motor behaviour in patients with Parkinson's disease.
Following cued levodopa (LD) intake, endurance exercise showed a beneficial effect on scored motor performance in patients with Parkinson's disease (PD) in comparison with rest. This may result from an exercise induced increase in endogenous dopamine synthesis. As a result, beneficial effects on movement and reactivity may occur. To measure reactivity and motor performance in a repeated fashion with instrumental tasks after cued administration of soluble 200 mg of LD/50 mg of benserazide. PD patients consecutively performed paradigms, which assess reactivity and movement performance, after a standardised period of rest or of age-related, heart rate adapted endurance exercise on two consecutive days in a random order. Reactivity and execution of simple and complex motion series were significantly better following exercise than after rest. Endurance exercise has a beneficial effect on reactivity and movement behaviour in PD patients following cued application of LD probably due to an augmented synthesis and release of dopamine and other catecholamines and release in the prefrontal cortex, the nucleus accumbens and the basal ganglia. Small changes in catecholamine modulation of prefrontal cortex cells can have profound effects on the ability of the prefrontal cortex to guide behaviour. Previous exercise may also improve pedunculopontine nucleus function, which is involved in motor-related attention processes.


Protecting Europe from diseases: from the international sanitary conferences to the ECDC.
In the past few decades there has been increased integration of communicable disease policies in Europe. The historical roots of this process date back to the mid-nineteenth century, when national authorities realized that the cross-boundary spread of diseases cannot be only a matter of national governance but requires common agreements and regulations. In the early 1950s the structuring of the World Health Organization in regional offices further contributed to the definition of Europe as a unit for risk assessments and international health cooperation. More recently the consolidation of the European Union has provided new institutional bases for shaping communicable disease policies at the supranational level. This article reviews these different attempts to protect the European space from diseases. It is argued that changing modes of communicable disease control not only have reflected shifts in public health priorities and institutional contexts but have also been important loci where different understandings of Europe and European political identity emerged and were negotiated. Against this background the article then examines past achievements and future challenges of the current European framework and discusses implications for the wider process of European integration.


Dismutase-competent SOD1 mutant accumulation in myelinating Schwann cells is not detrimental to normal or transgenic ALS model mice.
Mutant superoxide dismutase 1 (SOD1) action within non-neuronal cells is implicated in damage to spinal motor neurons in a genetic form of amyotrophic lateral sclerosis (ALS). Central nervous system glial cells such as astrocytes and microglia drive progression in transgenic mutant SOD1 mice, however, the role of myelinating glia remains unclear. Specifically, peripheral myelinating glial cells are likely candidates for mediating degeneration of distal synapses and axons of motor neurons in ALS. Here, we examine the potential contribution of peripheral axon ensheathing Schwann cells to ALS by constructing transgenic mice expressing dismutase active mutant SOD1(G93A) driven by the myelin protein zero (P0) promoter. In this model, mutant SOD1 accumulation in Schwann cells was comparable to levels in mice ubiquitously expressing a SOD1(G93A) transgene that become paralysed. Growth, locomotion and survival of these P0-SOD1(G93A) mice were indistinguishable from normal animals. There was no evidence for spinal motor neuron loss, distal axonal degeneration and p75 neurotrophin receptor (p75(NTR)) upregulation in the periphery of P0-SOD1(G93A) mice, unlike transgenic SOD1(G93A) mice with presymptomatic p75(NTR) induction and death-signalling. Furthermore, Schwann cells were resistant to mutant SOD1 aggregation in vivo and in transfected primary cultures. Increasing mutant SOD1 synthesis in Schwann cells by cross-breeding transgenic P0-SOD1(G93A) and SOD1(G93A) mice did not affect disease onset or survival. We conclude that dismutase-competent mutant SOD1 accumulation within Schwann cells is not pathological to spinal motor neurons or deleterious to disease course in transgenic ALS model mice, in contrast to astrocytes and microglia.


Bridging inhaled aerosol dosimetry to physiologically based pharmacokinetic modeling for toxicological assessment: nicotine delivery systems and beyond.
One of the challenges for toxicological assessment of inhaled aerosols is to accurately predict their deposited and absorbed dose. Transport, evolution, and deposition of liquid aerosols are driven by complex processes dominated by convection-diffusion that depend on various factors related to physics and chemistry. These factors include the physicochemical properties of the pure substance of interest and associated mixtures, the physical and chemical properties of the aerosols generated, the interplay between different factors during transportation and deposition, and the subject-specific inhalation topography. Several inhalation-based physiologically based pharmacokinetic (PBPK) models have been developed, but the applicability of these models for aerosols has yet to be verified. Nicotine is among several substances that are often delivered via the pulmonary route, with varied kinetics depending upon the route of exposure. This was used as an opportunity to review and discuss the current knowledge and state-of-the-art tools combining aerosol dosimetry predictions with PBPK modeling efforts. A validated tool could then be used to perform for toxicological assessment of other inhaled therapeutic substances. The Science Panel from the Alliance of Risk Assessment have convened at the "Beyond Science and Decisions: From Problem Formulation to Dose-Response Assessment" workshop to evaluate modeling approaches and address derivation of exposure-internal dose estimations for inhaled aerosols containing nicotine or other substances. The discussion involved PBPK model evaluation criteria, challenges, and choices that arise in such a model design, development, and application as a computational tool for use in human toxicological assessments.


Robustness and efficiency in interconnected networks with changes in network assortativity.
In this study, the effect of assortativity on the robustness and efficiency of interconnected networks was investigated. This involved constructing a network that possessed the desired degree of assortativity. Additionally, an interconnected network was constructed wherein the assortativity between component networks possessed the desired value. With respect to single networks, the results indicated that a decrease in assortativity provided low hop length, high information diffusion efficiency, and distribution of communication load on edges. The study also revealed that excessive assortativity led to poor network performance. In the study, the assortativity between networks was defined and the following results were demonstrated: assortative connections between networks lowered the average hop length and enhanced information diffusion efficiency, whereas disassortative connections between networks distributed the communication loads of internetwork links and enhanced robustness. Furthermore, it is necessary to carefully adjust assortativity based on the node degree distribution of networks. Finally, the application of the results to the design of robust and efficient information networks was discussed.


Econometric approaches to epidemiologic data: relating endogeneity and unobserved heterogeneity to confounding.
The concepts of endogeneity and unobserved heterogeneity are well-known among econometricians. However, these issues are rarely addressed in epidemiologic studies. This paper explores these two concepts, their relationship to each other, and the implications for analysis in epidemiologic studies. An endogenous variable is defined as a predictor variable which is partly determined by factors within the model itself, while unobserved heterogeneity is conceptualized as a vector of missing variables acting through the error term. Under certain assumptions, the simultaneous existence of an endogenous variable and unobserved heterogeneity is shown to act in a manner analogous to confounding. Specifically, this occurs due to an association between the error term in the equation and the endogenous predictor variable. The accepted econometric solution to this problem is to replace the endogenous variable with an 'instrumental variable' which is not correlated with the error term and thus not susceptible to confounding. The validity of these concepts and of the proposed solution are discussed.


Expanding the spectrum of genes responsible for hereditary motor neuropathies.
Inherited peripheral neuropathies (IPNs) represent a broad group of genetically and clinically heterogeneous disorders, including axonal Charcot-Marie-Tooth type 2 (CMT2) and hereditary motor neuropathy (HMN). Approximately 60%-70% of cases with HMN/CMT2 still remain without a genetic diagnosis. Interestingly, mutations in HMN/CMT2 genes may also be responsible for motor neuron disorders or other neuromuscular diseases, suggesting a broad phenotypic spectrum of clinically and genetically related conditions. Thus, it is of paramount importance to identify novel causative variants in HMN/CMT2 patients to better predict clinical outcome and progression. We designed a collaborative study for the identification of variants responsible for HMN/CMT2. We collected 15 HMN/CMT2 families with evidence for autosomal recessive inheritance, who had tested negative for mutations in 94 known IPN genes, who underwent whole-exome sequencing (WES) analyses. Candidate genes identified by WES were sequenced in an additional cohort of 167 familial or sporadic HMN/CMT2 patients using next-generation sequencing (NGS) panel analysis. Bioinformatic analyses led to the identification of novel or very rare variants in genes, which have not been previously associated with HMN/CMT2 (ARHGEF28, KBTBD13, AGRN and GNE); in genes previously associated with HMN/CMT2 but in combination with different clinical phenotypes (VRK1 and PNKP), and in the SIGMAR1 gene, which has been linked to HMN/CMT2 in only a few cases. These findings were further validated by Sanger sequencing, segregation analyses and functional studies. These results demonstrate the broad spectrum of clinical phenotypes that can be associated with a specific disease gene, as well as the complexity of the pathogenesis of neuromuscular disorders.


The impact of the re-engineered world of health-care in Canada on nursing and patient outcomes.
The healthcare environment is knowledge driven and knowledge and human resource dependent. Despite the paucity of evidence on which to shape and evaluate organizational change, health-care in Canada has undergone many changes in the last 15 years. In the pursuit of enhanced productivity, healthcare administrators have turned to industrial and engineering models. Using available Canadian research and policy reports, and where necessary, American literature, this paper describes the impact of re-engineering on nursing and on the relationship between nursing and patient outcomes. It also identifies emerging trends and ways forward.


Shock, but no shift: Hospitals' responses to changes in patient insurance mix.
Medicaid reimburses healthcare providers for services at a lower rate than any other type of insurance coverage. To account for the burden of treating Medicaid patients, providers claim that they must cost-shift by raising the rates of individuals covered by private insurance. Previous investigations of cost-shifting has produced mixed results. In this paper, I exploit a disabled Medicaid expansion where crowd-out was complete to investigate cost-shifting. I find that hospitals reduce the charge rates of the privately insured. Given that Medicaid is expanding in several states under the Affordable Care Act, these results may alleviate cost-shifting concerns of the reform.


Lung complications are common in intensive care treated patients with pelvis fractures: a retrospective cohort study.
The incidence of severe respiratory complications in patients with pelvis fractures needing intensive care have not previously been studied. Therefore, the aims of this registry study were to 1) determine the number of ICU patients with pelvis fractures who had severe respiratory complications 2) whether the surgical intervention in these patients is associated with the pulmonary condition and 3) whether there is an association between lung complications and mortality. We hypothesized that acute hypoxic failure (AHF) and acute respiratory distress syndrome (ARDS) 1) are common in ICU treated patients with pelvis fractures, 2) are not related to the reconstructive surgery, or to 3) to mortality. All patients in the database cohort (n = 112), scheduled for surgical stabilization of pelvis ring and/or acetabulum fractures, admitted to the general ICU at Uppsala University Hospital between 2007 and 2014 for intensive care were included. The incidence of AHF/ARDS was 67 % (75/112 patients), i.e., the percentage of patients that at any period during the ICU stay fulfilled the AHF/ARDS criteria. The incidence of AHF was 44 % and incidence of ARDS was 23 %. The patients with AHF/ARDS had more lung contusions and pneumonia than the patients without AHF/ARDS. Overall, there were no significant changes in oxygenation variables associated with surgery. However, 23 patients with pre-operative normal lung status developed AHF/ARDS in relation to the surgical procedure, whereas 12 patients with AHF/ARDS normalized their lung condition. The patients who developed AHF/ARDS had a higher incidence of lung contusion (P = 0.04) and the surgical stabilization was performed earlier (5 versus 10 days) in these patients (P = 0.03). We found that the incidence of respiratory failure in ICU treated patients with pelvis fractures was high, that the procedure around surgical stabilization seems to be associated with a worsening in the respiratory function in patients with lung contusion, and that mortality was low and was probably not related to the respiratory condition. Study was registered at ISRCTN.org number, ISRCTN10335587 .


The chemistry of the fac-[Re(CO)2(NO)]2+ fragment in aqueous solution.
The anions [ReX3(CO)2(NO)]- (with X = Cl, 1; X = Br, 2) have been prepared with different counterions. Complex 1 was found to lose its chloride ligands in water within 24 h. The [Re(H2O)3(CO)2(NO)]2+ cation obtained after hydrolysis is a strong acid, which consequently undergoes a slow condensation reaction in water to form the very stable [Re(mu3-O)(CO)2(NO)]4 cluster 4 at pH > 2, that precipitates from the aqueous solution and is insoluble also in organic solvents. Fast deprotonation of [Re(H2O)3(CO)2(NO)]2+ did not lead to 4 but rather to the mononuclear species [Re(OH)(H2O)2(CO)2(NO)]+. Subsequent attack of OH- at a CO group resulted in the formation of a rhenacarboxylic acid and its carboxylate anion. For solutions of even higher pH, IR spectroscopy provided evidence for the formation of a Re(C(O)ON(O)) species. These processes were found to be reversible on lowering the pH. Starting from cluster 4 it was possible to obtain complexes of the types [ReX(CO)2(NO)L2] or [Re(CO)2(NO)L3](L2 = 2-picolinate, 2,2'-bipyridine, L-phenylalanate; L3 = tris(pyrazolyl)methane, 1,4,7-trithiacyclononane) in the presence of an acid in protic solvents, but only in low yields. In further synthetic studies, complexes 1 and 2 were found to be superior starting materials for substitution reactions to form [ReX(CO)2(NO)L2] or [Re(CO)2(NO)L3] complexes.


The power to detect recent fragmentation events using genetic differentiation methods.
Habitat loss and fragmentation are imminent threats to biological diversity worldwide and thus are fundamental issues in conservation biology. Increased isolation alone has been implicated as a driver of negative impacts in populations associated with fragmented landscapes. Genetic monitoring and the use of measures of genetic divergence have been proposed as means to detect changes in landscape connectivity. Our goal was to evaluate the sensitivity of Wright's F st, Hedrick' G'st , Sherwin's MI, and Jost's D to recent fragmentation events across a range of population sizes and sampling regimes. We constructed an individual-based model, which used a factorial design to compare effects of varying population size, presence or absence of overlapping generations, and presence or absence of population sub-structuring. Increases in population size, overlapping generations, and population sub-structuring each reduced F st, G'st , MI, and D. The signal of fragmentation was detected within two generations for all metrics. However, the magnitude of the change in each was small in all cases, and when N e was >100 individuals it was extremely small. Multi-generational sampling and population estimates are required to differentiate the signal of background divergence from changes in Fst , G'st , MI, and D associated with fragmentation. Finally, the window during which rapid change in Fst , G'st , MI, and D between generations occurs can be small, and if missed would lead to inconclusive results. For these reasons, use of F st, G'st , MI, or D for detecting and monitoring changes in connectivity is likely to prove difficult in real-world scenarios. We advocate use of genetic monitoring only in conjunction with estimates of actual movement among patches such that one could compare current movement with the genetic signature of past movement to determine there has been a change.


Yersinia infection and acute abdominal pain.
In 194 patients presenting with acute abdominal pain from whom sequential serum samples were taken, the frequency of yersiniosis, established serologically, was significantly higher (23%) than in 320 control subjects (2%). Yersiniosis occurred in 31% of patients with acute appendicitis. Acute-phase serum samples only, obtained in a further 307 patients, yielded a falsely low frequency of yersiniosis (4%). Y pseudotuberculosis was five times more common than Y enterocolitica, and Y pseudotuberculosis type IV was the most common serotype, accounting for 43% of Yersinia infections. Yersinia may play a more important part in the aetiology of acute abdominal pain, and particularly acute appendicitis, than has been previously appreciated. Antibody titres to both Y enterocolitica and Y pseudotuberculosis frequently rise late in infections causing abdominal pain. Consequently analysis of acute-phase serum samples alone leads to underdiagnosis of yersiniosis.


Anesthesia for Blalock-Taussig shunt and pacemaker placement in an adult patient with univentricular heart. Case report.
Univentricular heart is a complex, rare, and severe cardiopathy, with no possibility of curative surgical treatment, associated with a high mortality in the first years of life. The objective of this article was to describe a rare case of an adult patient with uncorrected single ventricle who was admitted for pulmonary valvuloplasty but was submitted to a modified Blalock-Taussig and placement of an epicardic pacemaker. The complementary objective of this report was to address the anesthetic particularities of adult patients with uncorrected congenital cardiopathy. CASE REPORT A 34 years old female patient, weighing 60 kg, with a complex congenital cardiopathy with a single ventricle, important infundibular pulmonary stenosis and moderate pulmonary hypertension was admitted to the hospital without conditions to undergo surgical correction. The patient had a history several therapeutic bleedings to treat polycythemia. She was admitted due to worsening hypoxemia, an episode of syncope, and recent onset of third degree atrioventricular block. On admission, the patient was hemodynamically stable, heart rate of 42 bpm, SpO2 73%, central cyanosis and cyanosis of the extremities, and blood pressure 120 x 70 mmHg. Cardiac catheterization and pulmonary valvuloplasty were proposed. Due to the impossibility of success of this technique, Blalock-Taussig procedure with placement of a pacemaker was indicated. The procedure was performed in the following day without intercurrences, and the patient was discharged 7 days after the surgery, with SpO2 85%, hematocrit 49%, and improvement of the dyspnea. The success of anesthesia for surgical correction of complex congenital cardiopathy requires knowledge on the pathophysiology of the disorder, as well as the particularities inherent to the anesthetic technique used.


Musculoskeletal profile of middle-aged Ving Tsun Chinese martial art practitioners: A cross-sectional study.
This cross-sectional exploratory study aimed to quantify and compare the axial and appendicular bone mineral density (BMD), muscle mass, and muscle strength of middle-aged practitioners of Ving Tsun (VT; a hard-style Chinese martial art) with those of nonpractitioners.Eighteen VT practitioners (mean age ± standard deviation = 51.8 ± 17.7 years; 12 men and six women) and 36 active controls (mean age ± standard deviation = 58.7 ± 11.0 years; 18 men and 18 women) participated in the study. All participants underwent a 1-day battery of musculoskeletal examinations. The BMD of the total radius, total hip, femoral neck, and lumbar spine was measured using dual-energy X-ray absorptiometry, as was the lean mass of the arm, leg, and trunk. Muscle strength of the upper and lower limbs was assessed using a Jamar dynamometer and an isokinetic dynamometer at 60°/second, respectively.VT-trained participants had a 11.5% higher total radius BMD (P = 0.023), a 17.8% higher leg lean mass (P = 0.014), a 56.4% higher isokinetic body weight-adjusted peak torque of the knee extensors (P < 0.001), a 60.8% higher isokinetic body weight-adjusted peak torque of knee flexors (P < 0.001), and a 31.4% shorter time to reach peak torque in the knee flexors (P = 0.001) than the active controls. No significant differences were found in any of the other musculoskeletal outcomes between the 2 groups (P > 0.05).Middle-aged VT practitioners displayed a higher total radius BMD and leg lean mass and better knee extensor and flexor muscular performances than their healthy active counterparts. Healthcare professionals may consider using this alternative method of training to improve the musculoskeletal health of middle-aged adults.


Increasing memory load modulates regional brain activity in older adults as measured by fMRI.
Several recent studies using functional magnetic resonance imaging (fMRI) during recognition memory tests have suggested that the ability to neuromodulate as a function of cognitive demand may be impaired in older adults due to age-related cell loss and neural volume reduction in memory specific regions. In the current study, older adults (ages 59-77) were tested with fMRI during a delayed-recognition task in which memory load for faces was varied across trials. Activity was greater in amplitude for three- versus one-face stimuli within the superior, middle, and inferior frontal gyri, intraparietal sulcus, and fusiform gyrus. It was concluded that the ability to modulate activity with increasing load is preserved in older adults despite reductions in neural volume.


Advanced approach to information security management system model for industrial control system.
Organizations make use of important information in day-to-day business. Protecting sensitive information is imperative and must be managed. Companies in many parts of the world protect sensitive information using the international standard known as the information security management system (ISMS). ISO 27000 series is the international standard ISMS used to protect confidentiality, integrity, and availability of sensitive information. While an ISMS based on ISO 27000 series has no particular flaws for general information systems, it is unfit to manage sensitive information for industrial control systems (ICSs) because the first priority of industrial control is safety of the system. Therefore, a new information security management system based on confidentiality, integrity, and availability as well as safety is required for ICSs. This new ISMS must be mutually exclusive of an ICS. This paper provides a new paradigm of ISMS for ICSs, which will be shown to be more suitable than the existing ISMS.


A randomized, open-label, multicentre, phase 2/3 study to evaluate the safety and efficacy of lumiliximab in combination with fludarabine, cyclophosphamide and rituximab versus fludarabine, cyclophosphamide and rituximab alone in subjects with relapsed chronic lymphocytic leukaemia.
Lumiliximab is a chimeric monoclonal antibody that targets CD23 on the surface of chronic lymphocytic leukaemia (CLL) B-cells. Early phase clinical studies with lumiliximab alone and in combination with fludarabine, cyclophosphamide and rituximab (FCR) established its potential efficacy and tolerability. The 152CL201 trial [Lumiliximab with fludarabine, cyclophosphamide and rituximab (FCR) versus FCR alone in subjects with relapsed CLL; LUCID] was a phase 2/3, randomized (1:1), open-label, multicentre study of lumiliximab in combination with FCR versus FCR alone in patients with relapsed CLL. Six hundred and twenty-seven patients were randomized to either arm. Overall the combination of lumiliximab with FCR was not significantly better than FCR alone (overall response rate 71% vs. 72%, complete response rate 16% vs. 15%, median progression-free survival 24.6 vs. 23.9 months respectively, for FCR with and without lumiliximab). There was a slightly increased incidence of adverse events with lumiliximab but these increases did not appear to lead to differences in eventual outcomes. An interim analysis failed to show sufficient efficacy of the combination of lumiliximab with FCR. The study was therefore stopped early for lack of efficacy. Despite the eventual outcome, the LUCID trial is one of the largest studies that provides valuable insight into the efficacy and tolerability of FCR as a therapeutic option for patients with relapsed CLL.


African swine fever virus AP endonuclease is a redox-sensitive enzyme that repairs alkylating and oxidative damage to DNA.
African swine fever virus (ASFV) encodes an AP endonuclease (pE296R) which is essential for virus growth in swine macrophages. We show here that the DNA repair functions of pE296R (AP endonucleolytic, 3'-->5' exonuclease, 3'-diesterase and nucleotide incision repair (NIR) activities) and DNA binding are inhibited by reducing agents. Protein pE296R contains one intramolecular disulfide bond, whose disruption by reducing agents might perturb the interaction of the viral AP endonuclease with the DNA substrate. The characterization of the 3'-->5' exonuclease and 3'-repair diesterase activities of pE296R indicates that it has strong preference for mispaired and oxidative base lesions at the 3'-termini of single-strand breaks. Finally, the viral protein protects against DNA damaging agents in both prokaryotic and eukaryotic cells, emphasizing its importance in vivo. The biochemical and genetic properties of ASFV AP endonuclease are consistent with the repair of DNA damage generated by the genotoxic intracellular environment of the host macrophage.


Zuo Jin Wan, a Traditional Chinese Herbal Formula, Reverses P-gp-Mediated MDR In Vitro and In Vivo.
Zuo Jin Wan (ZJW), a typical traditional Chinese medicine (TCM) formula, has been identified to have anticancer activity in recent studies. In this study, we determined the underlying mechanism of ZJW in the reversal effect of multidrug resistance on colorectal cancer in vitro and in vivo. Our results showed that ZJW significantly enhanced the sensitivity of chemotherapeutic drugs in HCT116/L-OHP, SGC7901/DDP, and Bel/Fu MDR cells. Moreover, combination of chemotherapy with ZJW could reverse the drug resistance of HCT116/L-OHP cells, increase the sensitivity of HCT116/L-OHP cells to L-OHP, DDP, 5-Fu, and MMC in vitro, and inhibit the tumor growth in the colorectal MDR cancer xenograft model. ICP-MS results showed that ZJW could increase the concentration of chemotherapeutic drugs in HCT116/L-OHP cells in a dose-dependent manner. Furthermore, we showed that ZJW could reverse drug resistance of colorectal cancer cells by decreasing P-gp level in vitro and in vivo, which has been represented as one of the major mechanisms that contribute to the MDR phenotype. Our study has provided the first direct evidence that ZJW plays an important role in reversing multidrug resistance of human colorectal cancer and may be considered as a useful target for cancer therapy.


Characterization of humoral and cellular immune responses elicited by a recombinant adenovirus serotype 26 HIV-1 Env vaccine in healthy adults (IPCAVD 001).
Adenovirus serotype 26 (Ad26) has been developed as a novel candidate vaccine vector for human immunodeficiency virus type 1 (HIV-1) and other pathogens. The primary safety and immunogenicity data from the Integrated Preclinical/Clinical AIDS Vaccine Development Program (IPCAVD) 001 trial, the first-in-human evaluation of a prototype Ad26 vector-based vaccine expressing clade A HIV-1 Env (Ad26.ENVA.01), are reported concurrently with this article. Here, we characterize in greater detail the humoral and cellular immune responses elicited by Ad26.ENVA.01 in humans. Samples from the IPCAVD 001 trial were used for humoral and cellular immunogenicity assays. We observed a dose-dependent expansion of the magnitude, breadth, and epitopic diversity of Env-specific binding antibody responses elicited by this vaccine. Antibody-dependent cell-mediated phagocytosis, virus inhibition, and degranulation functional activity were also observed. Env-specific cellular immune responses induced by the vaccine included multiple CD8(+) and CD4(+) T-lymphocyte memory subpopulations and cytokine secretion phenotypes, although cellular immune breadth was limited. Baseline vector-specific T-lymphocyte responses were common but did not impair Env-specific immune responses in this study. Ad26.ENVA.01 elicited a broad diversity of humoral and cellular immune responses in humans. These data support the further clinical development of Ad26 as a candidate vaccine vector. NCT00618605.


Impacts of 120 years of fertilizer addition on a temperate grassland ecosystem.
The widespread application of fertilizers has greatly influenced many processes and properties of agroecosystems, and agricultural fertilization is expected to increase even further in the future. To date, most research on fertilizer impacts has used short-term studies, which may be unrepresentative of long-term responses, thus hindering our capacity to predict long-term impacts. Here, we examined the effects of long-term fertilizer addition on key ecosystem properties in a long-term grassland experiment (Palace Leas Hay Meadow) in which farmyard manure (FYM) and inorganic fertilizer treatments have been applied consistently for 120 years in order to characterize the experimental site more fully and compare ecosystem responses with those observed at other long-term and short-term experiments. FYM inputs increased soil organic carbon (SOC) stocks, hay yield, nutrient availability and acted as a buffer against soil acidification (>pH 5). In contrast, N-containing inorganic fertilizers strongly acidified the soil (<pH 4.5) and increased surface SOC stocks by increasing the C stored in the coarse (2.8 mm-200 μm) and fine (200-50 μm) fractions. Application of N fertilizers also reduced plant species richness and the abundance of forbs and legumes. Overall, our results were broadly consistent with those observed in other very long-term studies (the Park Grass and Steinach Grassland experiments) in that fertilization effects on plant and soil properties appeared to be driven by differences in both nutrient input and changes to soil pH. We also established that the direction of long-term fertilization effects tended to be comparable with short-term experiments, but that their magnitude differed considerably, particularly where ammonium sulphate-induced acidification had occurred. We therefore conclude that short-term studies are unlikely to possess the required timeframe to accurately predict long-term responses, thus necessitating the use of long-term study sites. Such experiments should be strategically established in regions where future fertilizer use is expected to increase rapidly.


Rhesus monkeys: mating season mobility of adult males.
Groups of rhesus monkeys, heretofore described as closed social units, experience a seasonal exchange of a portion of the adult males. Male shifting corresponds with the season of mating, and results in copulation with females of newly joined groups. This pattern is socially disruptive, but provides opportunity for exchange of genetic material between groups of a region.


Testing a low-cost approach to giving eRIG for rabies PEP: Ethical issues.
Ethical concerns in using a lower dose of equine rabies immune globulin (eRIG) to irrigate wounds from dog bites to prevent rabies are discussed. A lower dose of eRIG was used because of a general shortage of eRIG and the high market cost in the Himachal Pradesh state of India. The cost and availability of drugs in low- and middle-income countries (LMIC) often necessitates testing a lower dose of a vaccine or treatment than that recommended by international organizations (eg WHO). It raises the issue that recommendations may be designed for higher income countries without taking into consideration issues of supply and cost. Secondly a case-control design to compare dosages or delivery systems is usually not an option so investigators must often use historical data for comparison or other study designs. The ethical issues in the testing of drugs and vaccines in LMIC must be continuously reviewed by the international community.


Complementary and alternative therapy use before and after breast cancer diagnosis: the Pathways Study.
Many women use complementary and alternative medicine (CAM) to maintain or improve their health. We describe CAM use among the first 1,000 participants enrolled in the Pathways Study, an ongoing prospective cohort study of women diagnosed with breast cancer (BC). Participants, identified by rapid case ascertainment in Kaiser Permanente Northern California, are women > or = 21 years diagnosed with first invasive BC. Comprehensive baseline data are collected on CAM use through in-person interviews. Study participants include 70.9% non-Hispanic whites, 10.2% Hispanics, 9.0% Asians, 6.5% African-Americans, and 3.4% others. Most women (82.2%) were diagnosed with AJCC stage I/II BC at average (+/-SD) age 59.5 (+/-12.0) years and reported prior use of at least one form of CAM (96.5% of participants). In the 5 years before diagnosis, CAM therapies used at least weekly by >20% of women included green tea, glucosamine, omega-3 fatty acids, prayer and religion. CAM use was high (86.1% of participants) in the period immediately following diagnosis; 47.5% used botanical supplements, 47.2% used other natural products, 28.8% used special diets, 64.2% used mind-body healing, and 26.5% used body/energy/other treatments. In multivariable analyses, frequent use of each CAM modality before and after diagnosis was associated with use of other CAM modalities and other health behaviors (i.e., high fruit/vegetable intake, lower BMI). CAM use before and after BC diagnosis is common in this diverse group of women. Our results emphasize the need for clinicians to discuss CAM use with all BC patients.


Lassa virus hepatitis: a study of fatal Lassa fever in humans.
In order to explore the significance of a previous observation that the most important pathologic changes in fatal Lassa fever are hepatic, we have studied postmortem liver biopsies from 19 patients with fatal Lassa fever. We observed a vigorous macrophage response to cellular damage, but we found no evidence of lymphocyte infiltration in infected hepatic tissues. Using semi-quantitative estimates of liver cell damage, we found a wide range in the severity and progression of Lassa virus hepatitis in our fatal cases. We have classified for descriptive purposes three general nosopoeitic phases: active hepatocellular injury (less than 20% necrosis), continued damage and early recovery, and mitotic activity representing hepatic recovery. We conclude that the liver goes through cellular injury, necrosis and regeneration and any or all may be present at death. In no instance was the degree of hepatic damage sufficient to implicate hepatic failure, and all three phases were represented among our cases. We conclude that the hepatitis of Lassa fever in humans is not the primary cause of death.


Intratumoral neoadjuvant immunotherapy using IL-12 and dendritic cells is an effective strategy to control recurrence of murine hepatocellular carcinoma in immunosuppressed mice.
Liver transplantation is accepted as an effective therapy for hepatocellular carcinoma (HCC). However, recurrence is one of the most fatal complications. The aim of this study is to evaluate the efficacy of intratumoral immunotherapy using IL-12 gene therapy and dendritic cell injection for the purpose of effective treatment for HCC under conditions of immunosuppression. We found that the combined immunotherapy significantly induced sustained and high amounts of intratumoral IL-12 and IFN-gamma proteins and that it induced high HCC-specific CTL activity under immunosuppression as compared with each monotherapy or control. The combined immunotherapy also exerted effective antitumor effects on the immunosuppressed host, resulting in significant suppression of growth of the s.c. established tumor and complete suppression of lung and liver metastasis, without rejection of a fully allogeneic skin graft. These antitumor effects were dependent on both T cells and NK cells. Noteworthily, the combined intratumoral immunotherapy and tumor resection (that is, neoadjuvant immunotherapy) resulted in achievement of tumor-free and long-term survival of the some immunosuppressed mice, even when the mice were challenged with i.v. injection of HCC at the time of tumor resection. In contrast, all of the mice treated with neoadjuvant immunotherapy using monotherapy or control therapy suffered from lung and liver metastasis. These results suggest that intratumoral neoadjuvant immunotherapy using IL-12 gene therapy and dendritic cell therapy is a potent effective strategy to control recurrence of HCC in patients after liver transplantation for HCC and may be applicable to general cancer treatment.


Identifying inequitable healthcare in older people: systematic review of current research practice.
There is growing consensus on the importance of identifying age-related inequities in the receipt of public health and healthcare interventions, but concerns regarding conceptual and methodological rigour in this area of research. Establishing age inequity in receipt requires evidence of a difference that is not an artefact of poor measurement of need or receipt; is not warranted on the grounds of patient preference or clinical safety; and is judged to be unfair. A systematic, thematic literature review was undertaken with the objective of characterising recent research approaches. Studies were eligible if the population was in a country within the Organisation for Economic Co-operation and Development and analyses included an explicit focus on age-related patterns of healthcare receipt including those 60 years or older. A structured extraction template was applied. Extracted material was synthesised in thematic memos. A set of categorical codes were then defined and applied to produce summary counts across key dimensions. This process was iterative to allow reconciliation of discrepancies and ensure reliability. Forty nine studies met the eligibility criteria. A wide variety of concepts, terms and methodologies were used across these studies. Thirty five studies employed multivariable techniques to produce adjusted receipt-need ratios, though few clearly articulated their rationale, indicating the need for great conceptual clarity. Eighteen studies made reference to patient preference as a relevant consideration, but just one incorporated any kind of adjustment for this factor. Twenty five studies discussed effectiveness among older adults, with fourteen raising the possibility of differential effectiveness, and one differential cost-effectiveness, by age. Just three studies made explicit reference to the ethical nature of healthcare resource allocation by age. While many authors presented suitably cautious conclusions, some appeared to over-stretch their findings concluding that observed differences were 'inequitable'. Limitations include possible biases in the retrieved material due to inconsistent database indexing and a focus on OECD country populations and studies with English titles. Caution is needed among clinicians and other evidence-users in accepting claims of healthcare 'ageism' in some published papers. Principles for improved research practice are proposed.


Pathogenesis of Neisseria gonorrhoeae in the female reproductive tract: neutrophilic host response, sustained infection, and clinical sequelae.
Gonorrhea is a major global health concern, caused by the bacterium Neisseria gonorrhoeae. The main clinical feature of acute gonorrhea is neutrophilic influx that is unable to clear infection. Women of reproductive age are predominantly at risk for serious sequelae of gonorrhea, including pelvic inflammatory disease, ectopic pregnancy, and infertility. This review will highlight how neutrophils are recruited to the female reproductive tract (FRT) in response to N. gonorrhoeae, how N. gonorrhoeae resists killing by neutrophils, and the connection between neutrophilic inflammation and cellular damage. Epithelial cells and immune cells of the FRT recognize and respond to N. gonorrhoeae lipid A and heptose bisphosphate of lipooligosaccharide, porin, lipoproteins, and peptidoglycan fragments. N. gonorrhoeae skews the resulting immune response toward a neutrophilic, Th17-like response. N. gonorrhoeae has multiple, nonredundant mechanisms to survive inside neutrophils and in neutrophil extracellular traps. Infection that ascends to the upper FRT induces the further release of inflammatory cytokines and matrix metalloproteinases, which cause epithelial damage. N. gonorrhoeae is remarkable in its ability to recruit neutrophils, yet survive in their midst. New models being developed for FRT infection with N. gonorrhoeae will be useful to reveal the mechanisms underlying these observations.


The effect of beta adrenergic blockade on the carotid body response to hyperkalaemia in the cat.
Arterial chemoreceptor discharge and ventilation are both significantly increased when the concentration of arterial potassium is raised to a level typical of moderate exercise. However, although the plasma potassium level of exercising, beta-blocked patients rises by more than that of normal subjects, this does not show up in their steady-state ventilatory response, i.e. exercising beta-blocked subjects ventilate no more than exercising controls. The present experiments were designed to test the hypothesis that the apparent failure of beta-blocked subjects to respond to the extra hyperkalaemia that they experience might be accounted for by a reduction in the sensitivity of arterial chemoreceptors to potassium. We used eleven pentobarbitone-anaesthetized, thoracotomized, artificially hyperventilated cats, in which arterial potassium was raised from ca. 4.5 to ca. 7 mM before and during beta blockade by propranolol or atenolol. The steady-state relation between chemoreceptor discharge and arterial potassium was curvilinear, discharge becoming more sensitive to potassium as the concentration of the latter was raised. Beta blockade significantly reduced discharge at all levels of plasma potassium (P less than 0.0001). It also significantly reduced (P less than 0.05) the slope of the response of discharge to a given increase of plasma potassium. Our results show that beta blockade decreases the sensitivity of arterial chemoreceptors to increases in arterial potassium. This may explain why exercising beta-blocked subjects breathe no harder than controls, in spite of the fact that they are more hyperkalaemic.


Diverse protein regulations on PHA formation in Ralstonia eutropha on short chain organic acids.
Organic acids are considered as potential substrates for biosynthesis of polyhydroxyalkaonates. The acids may also be the metabolic inhibitors at moderate concentration levels. In this study, Ralstonia eutropha was used to elucidate the protein regulations when the bacterial cells pre-cultivated on glucose were exposed to three representative short chain organic acids, acetic, propionic and levulinic acids. The research compared and examined the proteins that might participate in PHA metabolism, primary metabolism, and cell's defense systems. A number of proteins were found to be induced in R. eutropha by using 1D-PAGE and nano-liquid chromatography tandem MS/MS. With the proteins being up-regulated, a dramatic change occurred in the induction of PHA metabolism, including fatty acid biosynthesis for acetate, beta-oxidation for propionate and both for levulinic acid. Acetate kinase was induced in response to the presence of acetate or levulinic acid. The organic acids induced several proteins involved in amino acid biosynthesis, purine and pyrimidine biosynthesis, and cofactor biosynthesis in R. eutropha, but the regulations had a great variation. R. eutropha might employ different regulation mechanisms to maintain cell growth and PHA formation when the cells are exposed to the organic acids as sole source of carbon and energy.


The effects of bibliotherapy on the mental well-being of informal caregivers of people with neurocognitive disorder: A systematic review and meta-analysis.
The number of people with neurocognitive disorder is increasing, and the majority of them are cared for by informal caregivers in the community. Mental health problems are common among caregivers, however, professional support for them is often limited. Non-pharmacological self-help interventions, such as bibliotherapy, may improve mental well-being and has the potential for being integrated into clinical or social services. To explore what types of bibliotherapy have been used for improving the mental well-being of informal caregivers of people with neurocognitive disorders, and the effect on mental well-being outcomes. A systematic review and meta-analysis. Six databases were searched for relevant articles on July 1, 2019. Clinical trial registries and the reference lists of included studies were also searched. Both randomized controlled trials and quasi-experimental studies were included. The Cochrane Collaboration risk of bias tool for randomized controlled trials was used to assess the quality of studies. Review Manager 5.3 was used to analyze data, standardized mean difference (SMD) and 95% confidence interval (CI) were used to estimate the pooled treatment effect. Random effects models were used for meta-analyses. Funnel plot was not performed due to the limited number of studies. This systematic review was registered at PROSPERO (CRD42019129152). Nine randomized controlled trials with 1036 informal caregivers were included. Most of the included studies had some aspects of bias. Three types of bibliotherapy were used. Bibliotherapy had a significant pooled medium to large effect on reducing depression at Z = 1.99 (SMD = -0.74, 95%CI = -1.47 to -0.01, p = .05), however, the heterogeneity was high (I2 = 94%). For the subgroups, only the video-based bibliotherapy significantly reduced depression at Z = 2.78 (I2 = 83%, SMD = -2.11, 95%CI = -3.6 to -0.62, p = .005). Bibliotherapy had a significant small to medium effect on caregiver's self-efficacy for dealing with problem behaviours at Z = 2.44 (I2 = 0, SMD = 0.36, 95%CI = 0.05 to 0.67, p = .02), however, the effect on self-efficacy for obtaining respite was not significant (I2 = 0, SMD = 0.17, 95%CI = -0.16 to 0.49, p = .32). The effect on decreasing state anxiety was significant at Z = 2.30 (I2 = 22%, SMD = -0.22, 95% CI = -0.41 to -0.33, p = .02). Bibliotherapy showed positive effects on reducing depression, improving self-efficacy for dealing with problem behaviors and reducing anxiety among informal caregivers. The effects on reducing depression should be viewed with caution due to high heterogeneity. The effects on other mental well-being outcomes are inconclusive due to limited number of studies and this underscores the need for further research.


A new-style, slotted-cymbal transducer with large displacement and high energy transmission.
The cymbal transducer had more improved performances than the moonie transducer, but as with the moonie end caps, flexural motion of the cymbal end caps would cause high-tangential stresses, which could lead to loss of mechanical output energy. So, a new-style design, called slotted-cymbal transducer, is presented in this paper. The slotted-cymbal transducer released the tangential stresses by adopting a new-style, radial-slotted cymbal end caps. Through theoretical calculation and finite element analysis in collaboration with measurements, the slotted-cymbal transducer was demonstrated to possess high performances of displacement and energy transmission. This design would decrease the fundamental resonance frequencies of systems by different numbers of slots, and it would have more potential applications of low frequency and large displacement.


HuR: a promising therapeutic target for angiogenesis.
Multiple angiogenic factors and inhibitors are becoming potential therapeutic targets for ischemia diseases and cancer. Posttranscriptional regulation through the untranslated region of mRNA is emerging as a critical regulating level in nearly all the biological processes. As a kind of RNA binding proteins, HuR plays important role in augmenting the hypoxic or inflammatory signal, stabilizing the resultant angiogenic factors and promoting the proliferation and migration of endothelial cells. These implicate HuR in the proangiogenic factors mediated angiogenesis in the hypoxia and inflammatory. We consider hypotheses that a more effective angiogenesis can be acquired through strengthened and prolonged effects of angiogenic factors, and that progresses in therapeutic angiogensis might also shed light on the implication of HuR in blocking tumor angiogensis. These considerations may help us to explain HuR as a promising therapeutic target for angiogenesis related disease. It may be a candidate in hypoxia therapy and cancer management.


Biodegradation of microcystins during gravity-driven membrane (GDM) ultrafiltration.
Gravity-driven membrane (GDM) ultrafiltration systems require little maintenance: they operate without electricity at ultra-low pressure in dead-end mode and without control of the biofilm formation. These systems are already in use for water purification in some regions of the world where adequate treatment and distribution of drinking water is not readily available. However, many water bodies worldwide exhibit harmful blooms of cyanobacteria that severely lower the water quality due to the production of toxic microcystins (MCs). We studied the performance of a GDM system during an artificial Microcystis aeruginosa bloom in lake water and its simulated collapse (i.e., the massive release of microcystins) over a period of 21 days. Presence of live or destroyed cyanobacterial cells in the feed water decreased the permeate flux in the Microcystis treatments considerably. At the same time, the microbial biofilms on the filter membranes could successfully reduce the amount of microcystins in the filtrate below the critical threshold concentration of 1 µg L(-1) MC for human consumption in three out of four replicates after 15 days. We found pronounced differences in the composition of bacterial communities of the biofilms on the filter membranes. Bacterial genera that could be related to microcystin degradation substantially enriched in the biofilms amended with microcystin-containing cyanobacteria. In addition to bacteria previously characterized as microcystin degraders, members of other bacterial clades potentially involved in MC degradation could be identified.


Sexual behaviours and sexual health outcomes among young adults with limiting disabilities: findings from third British National Survey of Sexual Attitudes and Lifestyles (Natsal-3).
To explore whether the sexual behaviours and sexual health outcomes of young adults with self-reported disabilities that they perceive limit their activities ('limiting disability') differ from those without disability. Complex survey analyses of cross-sectional probability sample survey data collected between September 2010 and August 2012 using computer-assisted personal interviewing and computer-assisted self-interview. British general population. 7435 women and men aged 17-34 years, resident in private households in Britain, interviewed for the third National Survey of Sexual Attitudes and Lifestyles. Self-reported sexual behaviour and sexual health outcomes. Approximately 1 in 10 participants reported having a limiting disability. Sexual behaviours were similar between those with limiting disability and those without, with a few exceptions. Women and men with limiting disability were less likely to report having sexual partner(s) (past year, adjusted ORs (AORs) for age and social class: AORs: 0.71, 0.75, respectively). Women with limiting disability were more likely to report having same-sex partner(s) in the past 5 years (AOR: 2.39). Differences were seen in sexual health outcomes, especially among women; those with limiting disability were more likely to report having experienced non-volitional sex (ever, AOR: 3.08), STI diagnoses (ever, AOR: 1.43) and sought help/advice regarding their sex life (past year, AOR: 1.56). Women with limiting disability were also more likely to feel distressed/worried about their sex life than those without limiting disability (AORs: 1.61). None of these associations were seen in men. Young adults with limiting disability, especially women, are more likely to report adverse sexual health outcomes than those without, despite comparatively few behavioural differences. It is important to ensure that people with disabilities are included in sexual health promotion and service planning, and targeted policy and programme interventions are needed to address negative sexual health outcomes disproportionally experienced by people with disabilities.


Out-of-pocket costs, primary care frequent attendance and sample selection: Estimates from a longitudinal cohort design.
This paper examines the effect of out-of-pocket costs on subsequent frequent attendance in primary care using data from the Personality and Total Health (PATH) Through Life Project, a representative community cohort study from Canberra, Australia. The analysis sample comprised 1197 respondents with two or more GP consultations, and uses survey data linked to administrative health service use (Medicare) data which provides data on the number of consultations and out-of-pocket costs. Respondents identified in the highest decile of GP use in a year were defined as Frequent Attenders (FAs). Logistic regression models that did not account for potential selection effects showed that out-of-pocket costs incurred during respondents' prior two consultations were significantly associated with subsequent FA status. Respondents who incurred higher costs ($15-$35; or >$35) were less likely to become FAs than those who incurred no or low (<AUS$15 per consultation) costs, with no difference evident between the no and low-cost groups. However, a counterfactual model that adjusted for factors associated with the selection into payment levels did not find an influence of payment, with only a non-significant gradient in the expected direction. Hence these findings raise doubts that price drives FA behaviour, suggesting that co-payments are unlikely to affect the number of GP consultations amongst frequent attenders.


OKT3 induction via idiotypic networks of mirror-image immunosuppressive antiimmunoglobulins in renal transplant recipients.
Four of 21 renal transplant recipients treated with OKT3 for rejection episodes developed a second sustained (approximately 2 weeks) depression in CD3 peripheral blood lymphocyte cell-surface-marker expression. This occurred after OKT3 therapy had ceased, subsequent to a return toward baseline CD3 levels seen before OKT3 therapy was instituted. The second decrease in CD3 T cell counts was dissociated from CD2 marker T cell counts using flow cytometry and coincided with transient cytomegaloviral infections. Three phases of immunosuppression were defined in these 4 patients: phase I (during OKT3 treatment); phase II (after treatment when CD3 counts were reconstituted); and phase III (when CD3 counts again were depressed). During phase III, serum of the 4 affected patients could transfer a blocking effect on the expression of the CD3 marker of peripheral blood T cells of "normal" laboratory volunteers. Contained in these sera were human IgG antibodies that bound on Western blot analysis and by radioautography after immunoprecipitation to a protein band of a T cell membrane lysate with an m.w. of 23 kD. The reaction was identical to that seen with OKT3 (immunoprecipitation). Moreover, this Western blot binding could be virtually (but not completely) eliminated by multiple absorptions of the T cell membrane lysate with OKT3. By using an affinity-purified human anti-OKT3 IgG from one of the 4 patients, it was possible to immunoabsorb from phase III sera the CD3 blocking activity as well as the binding to the 23 KD protein band. A reverse immune absorption by the phase III sera with the anti-OKT3 IgG after ultracentrifugation prevented the anti-OKT3 IgG from binding to OKT3 coated plates in solid-phase radioimmunoassay. These data support the notion that autoimmune human anti-anti-id (Ab2) antibodies can occasionally be generated by treatment with OKT3, which are directed against CD3 complex epitopes similar to the ligand of OKT3.


Crystal structure of the NanB sialidase from Streptococcus pneumoniae.
The Streptococcus pneumoniae genomes encode up to three sialidases (or neuraminidases), NanA, NanB and NanC, which are believed to be involved in removing sialic acid from host cell surface glycans, thereby promoting colonization of the upper respiratory tract. Here, we present the crystal structure of NanB to 1.7 A resolution derived from a crystal grown in the presence of the buffer Ches (2-N-cyclohexylaminoethanesulfonic acid). Serendipitously, Ches was found bound to NanB at the enzyme active site, and was found to inhibit NanB with a K(i) of approximately 0.5 mM. In addition, we present the structure to 2.4 A resolution of NanB in complex with the transition-state analogue Neu5Ac2en (2-deoxy-2,3-dehydro-N-acetyl neuraminic acid), which inhibits NanB with a K(i) of approximately 0.3 mM. The sulphonic acid group of Ches and carboxylic acid group of Neu5Ac2en interact with the arginine triad of the active site. The cyclohexyl group of Ches binds in the hydrophobic pocket of NanB occupied by the acetamidomethyl group of Neu5Ac2en. The topology around the NanB active site suggests that the enzyme would have a preference for alpha2,3-linked sialoglycoconjugates, which is confirmed by a kinetic analysis of substrate binding. NMR studies also confirm this preference and show that, like the leech sialidase, NanB acts as an intramolecular trans-sialidase releasing Neu2,7-anhydro5Ac. All three pneumoccocal sialidases possess a carbohydrate-binding domain that is predicted to bind sialic acid. These studies provide support for a possible differential role for NanB compared to NanA in pneumococcal virulence.


Engaging minority high school students as health disparities interns: findings and policy implications of a summer youth pipeline program.
The purpose of this paper was to describe the development and implementation of a health disparities summer internship program for minority high school students that was created to increase their knowledge of health disparities, provide hands-on training in community-engaged research, support their efforts to advocate for policy change, and further encourage youth to pursue careers in the health professions. Fifty-one high school students who were enrolled in a well-established, science-enrichment after-school program in Brooklyn, New York, participated in a 4-week summer internship program. Students conducted a literature review, focus groups/interviews, geographic mapping or survey development that focused on reducing health disparities at 1 of 15 partnering CBOs. Overall, student interns gained an increase in knowledge of racial/ethnic health disparities. There was a 36.2% increase in students expressing an interest in pursuing careers in minority health post program. The majority of the participating CBOs were able to utilize the results of the student-led research projects for their programs. In addition, research conclusions and policy recommendations based on the students' projects were given to local elected officials. As demonstrated by our program, community-academic partnerships can provide educational opportunities to strengthen the academic pipeline for students of color interested in health careers and health disparities research.


Measuring the digital divide among people with severe mental ill health using the essential digital skills framework.
Amid the vast digitalisation of health and other services during the pandemic, people with no digital skills are at risk of digital exclusion. This risk might not abate by the end of the pandemic. This article seeks to understand whether people with severe mental ill health (SMI) have the necessary digital skills to adapt to these changes and avoid digital exclusion. Two hundred and forty-nine adults with SMI across England completed a survey online or offline. They provided information on their digital skills based on the Essential Digital Skills (EDS) framework, sociodemographic information, and digital access. This is the first time that the EDS is benchmarked in people with SMI. 42.2% had no Foundation Skills, and 46.2% lacked skills for daily life (lacking Foundation or Life Skills). 23.0% of those working lacked skills for professional life (lacking Foundation or Work Skills). The most commonly missing skills were handling passwords and using the device settings (Foundation Skills) and online problem solving (Skills for Life). People were interested in learning more about approximately half of the skills they did not have. People were more likely to lack Foundation Skills if they were older, not in employment, had a psychosis-spectrum disorder, or had no Internet access at home. A significant portion of people with SMI lacked Foundation Skills in this objective and benchmarked survey. This points to a high risk for digital exclusion and the need for focused policy and tailored health sector support to ensure people retain access to key services and develop digital skills and confidence. To our knowledge, this is the first time this has been described using the EDS framework. Services, including the National Health Service (NHS), need to be aware of and mitigate the risks.


Suppressor cells: dependence on assay conditions for functional activity.
Spleen cells educated in vitro with sheep red blood cells (SRBC) suppressed the plaque-forming cell response of Mishell-Dutton assay cultures challenged with optimal doses of SRBC. Changing conditions in the assay cultures changed the effect educated cells had on the assay culture responses. For example, educated cells helped rather than suppressed assay cultures of suboptimal numbers of spleen cells. Similarly, augmentation resulted upon addition of educated cells to assay cultures challenged with suboptimal doses of SRBC. Such a reversal of regulatory effects was not observed when assay cultures were challenged with supraoptimal antigen doses. Educated cells helped assay cultures of B spleen cells, and the addition of normal T cells reinstated suppression. Furthermore, maintenance of assay cultures under stationary rather than the usual rocking conditions allowed educated cells to help rather than suppress the antibody response of assay cultures. These results show that when the response of the target population (assay cultures) is low, the regulator (educated) cells augment the response, and vice versa, supporting the hypothesis that the effect regulator cells produce depends on the activity of the cells they regulate.


Differences in neutralization of simian lentivirus (SIVMAC) in lymphocyte and macrophage cultures.
Comparison of neutralization of SIVmac251 in primary macrophage cultures with neutralization in lymphocytes (CEM174 cells) showed that neutralizing antibodies induced by SIV251 in infected rhesus macaques protected both macrophages and T lymphocytes against infection when the virus was preincubated with the antibodies. In macrophages, the neutralizing antibodies also protected against infection when added 1 hour after the virus. Addition of antisera to macrophages between 24 and 48 hours after virus inoculation resulted in infection with continuous release of small amounts of p24 into the supernatant fluids but these antibody-treated cultures failed to exhibit cytopathic virus replication. In contrast, the same neutralizing antisera did not protect lymphocytes against infection and subsequent cytopathic replication of the virus when added only 1 hour after virus inoculation. This distinction in the effect that neutralizing antibodies had on the development of cytopathic infection in lymphocytes and macrophages when added after virus inoculation, suggests that they could alter the dynamics of virus replication and therefore the pathogenesis of disease.


DNA interchain cross-links formed by acrolein and crotonaldehyde.
Acrolein and higher alpha,beta-unsaturated aldehydes are bifunctional genotoxins. The deoxyguanosine adduct of acrolein, 3-(2-deoxy-beta-d-erythro-pentofuranosyl)-5,6,7,8-tetrahydro-8-hydroxypyrimido[1,2-a]purin-10(3H)-one (8-hydroxy-1,N(2)-propanodeoxyguanosine, 2a), is a major DNA adduct formed by acrolein. The potential for oligodeoxynucleotide duplexes containing 2a to form interchain cross-links was evaluated by HPLC, CZE, MALDI-TOF, and melting phenomena. Interchain cross-links represent one of the most serious types of damage in DNA since they are absolute blocks to replication. In oligodeoxynucleotides containing the sequence 5'-dC-2a, cross-linking occurred in a slow, reversible manner to the extent of approximately 50%. Enzymatic digestion to form 3-(2-deoxy-beta-d-erythro-pentofuranosyl)-5,6,7,8-tetrahydro-8-(N(2)-2'-deoxyguanosinyl)pyrimido[1,2-a]purin-10(3H)one (5a) and reduction with NaCNBH(3) followed by enzymatic digestion to give 1,3-bis(2'-deoxyguanosin-N(2)-yl)propane (6a) established that cross-linking had occurred with the exocyclic amino group of deoxyguanosine. It is concluded that the cross-link is a mixture of imine and carbinolamine structures. With oligodeoxynucleotide duplexes containing the sequence 5'-2a-dC, cross-links were not detected by the techniques enumerated above. In addition, (15)N-(1)H HSQC and HSQC-filtered NOESY spectra carried out with a duplex having (15)N-labeling of the target amino group established unambiguously that a carbinolamine cross-link was not formed. The potential for interchain cross-link formation by the analogous crotonaldehyde adduct (2b) was evaluated in a 5'-dC-2b sequence. Cross-link formation was strongly dependent on the configuration of the methyl group at C6 of 2b. The 6R diastereomer of 2b formed a cross-link to the extent of 38%, whereas the 6S diastereomer cross-linked only 5%.


Evaluation of myocardial deformation in patients with Kawasaki disease using speckle-tracking echocardiography during mid-term follow-up.
Speckle-tracking echocardiography is a recently developed technique for the evaluation of myocardial deformation or strain. Our objective was to examine strain through a mid-term follow-up of patients with Kawasaki disease. We explored left ventricular mechanics using speckle-tracking echocardiography in 35 patients with a history of Kawasaki disease at least 6 months after the acute phase. We also included 30 healthy children as controls. Strain data sets were acquired for the quantification of left ventricular global strain, segmental strain, and left ventricular ejection fraction. The mean age of our patients was 25.6±15.4 months. At a median follow-up of 57.5 months (16.5-98.2), although both values were in the normal range, the mean left ventricular ejection proportion of patients (57.3%) was a little lower than that of controls (p⩽0.05). Patient strain values at the basal inferoseptal (20.0), basal anterolateral (19.5), apical septal (23.3), and apical inferior (24.0) segments were lower compared with controls. In all, seven patients had coronary aneurysms during follow-up. Kawasaki disease patients with pyuria had lower left ventricular strain at the mid anterior, mid anteroseptal, apical anterior, and apical inferior segments and global longitudinal strain compared with patients with no pyuria (p⩽0.05). In children with a history of Kawasaki disease, impairment of left ventricular mechanics occurs especially within the left anterior descending artery territories.


Improved kidney graft function after preservation using a novel hypothermic machine perfusion device.
To study graft function and ischemia/reperfusion injury of porcine kidneys after preservation with the new Groningen Machine Perfusion (GMP) system versus static cold storage (CS). The increasing proportion of marginal and nonheart beating donors necessitates better preservation methods to maintain adequate graft viability. Hypothermic machine preservation (HMP) is a promising alternative to static CS. We have therefore developed and tested an HMP device, which is portable and actively oxygenates the perfusate via an oxygenator. The aim of the present study was to examine the efficacy of the GMP system in a transplantation experiment. In a porcine autotransplantation model, kidneys were retrieved and either cold stored in University of Wisconsin CS for 20 hours at 4 degrees C or subjected to HMP using University of Wisconsin machine perfusion at 4 degrees C with 2 different pressure settings: 30/20 mm Hg or 60/40 mm Hg. HMP at 30/20 mm Hg was found to better preserve the viability of kidneys reflected by improved cortical microcirculation, less damage to the proximal tubule, less damage mediated by reactive oxygen species, less proinflammatory cytokine expression, and better functional recovery after transplantation. However, high perfusion pressures (60/40 mm Hg) resulted in higher expression of von Willebrand factor and monocyte chemotactic peptide-1 in postpreservation biopsies and subsequent graft thrombosis in 2 kidneys. It is concluded that the GMP system improves kidney graft viability and perfusion pressures are critically important for outcome.


[Group interventions for people with refractory psychosis].
Various types of group interventions exist for people with severe mental disorders such as schziophrenia. The content and theoretical backgrounds vary according to the therapeutic goals as well as the clientele targeted. This article describes three group interventions : 1) one aiming at improving self-esteem, 2) one aiming at improving competence through stress management, and 3) one aiming at diminushing distress linked to psychotic symptoms with cognitive behavior therapy. Details on how to conduct these three group interventions, as well as their clinical and theoretical relevance for individuals with refractory psychosis will be described.


The LIPPSMAck POP (Lung Infection Prevention Post Surgery - Major Abdominal - with Pre-Operative Physiotherapy) trial: study protocol for a multi-centre randomised controlled trial.
Post-operative pulmonary complications are a significant problem following open upper abdominal surgery. Preliminary evidence suggests that a single pre-operative physiotherapy education and preparatory lung expansion training session alone may prevent respiratory complications more effectively than supervised post-operative breathing and coughing exercises. However, the evidence is inconclusive due to methodological limitations. No well-designed, adequately powered, randomised controlled trial has investigated the effect of pre-operative education and training on post-operative respiratory complications, hospital length of stay, and health-related quality of life following upper abdominal surgery. The Lung Infection Prevention Post Surgery - Major Abdominal- with Pre-Operative Physiotherapy (LIPPSMAck POP) trial is a pragmatic, investigator-initiated, bi-national, multi-centre, patient- and assessor-blinded, parallel group, randomised controlled trial, powered for superiority. Four hundred and forty-one patients scheduled for elective open upper abdominal surgery at two Australian and one New Zealand hospital will be randomised using concealed allocation to receive either i) an information booklet or ii) an information booklet, plus one additional pre-operative physiotherapy education and training session. The primary outcome is respiratory complication incidence using standardised diagnostic criteria. Secondary outcomes include hospital length of stay and costs, pneumonia diagnosis, intensive care unit readmission and length of stay, days/h to mobilise >1 min and >10 min, and, at 6 weeks post-surgery, patient reported complications, health-related quality of life, and physical capacity. The LIPPSMAck POP trial is a multi-centre randomised controlled trial powered and designed to investigate whether a single pre-operative physiotherapy session prevents post-operative respiratory complications. This trial standardises post-operative assisted ambulation and physiotherapy, measures many known confounders, and includes a post-discharge follow-up of complication rates, functional capacity, and health-related quality of life. This trial is currently recruiting. Australian New Zealand Clinical Trials Registry number: ACTRN12613000664741 , 19 June 2013.


A Silurian maxillate placoderm illuminates jaw evolution.
The discovery of Entelognathus revealed the presence of maxilla, premaxilla, and dentary, supposedly diagnostic osteichthyan bones, in a Silurian placoderm. However, the relationship between these marginal jaw bones and the gnathal plates of conventional placoderms, thought to represent the inner dental arcade, remains uncertain. Here we report a second Silurian maxillate placoderm, which bridges the gnathal and maxillate conditions. We propose that the maxilla, premaxilla, and dentary are homologous to the gnathal plates of placoderms and that all belong to the same dental arcade. The gnathal-maxillate transformation occurred concurrently in upper and lower jaws, predating the addition of infradentary bones to the lower jaw.


Leukotrienes affect secretory function of ovarian cells in vitro.
The aim of this study was to determine which cells are the source of production and target for leukotriene (LTs) action within the bovine ovary. Luteal (CL, days 14-16 of the oestrous cycle), steroidogenic cells (LSC) and endothelial cells (LEC) of the bovine corpus luteum (CL), and granulosa cells (GC) were isolated enzymatically, cultured in a monolayer and incubated with LTC(4), LTB(4), Azelastine (an antagonist of LTC(4)) or Dapsone (an antagonist of LTB(4)). Then cells were collected for determination of mRNA expression for LT receptors (LTRs) and 5-lipoxygenase (5-LO) by real time RT-PCR, and media were collected for determination of prostaglandin (PG)E(2), F(2α), progesterone (P4; LSC only), endothelin-1 (ET-1; LEC only) and 17-β oestradiol (E2; GC only). The greatest mRNA expression for LTR-II and 5-LO were found in LEC, whereas LTR-I mRNA expression did not differ among cell types. The level of PGE(2) increased after LTs treatment in each type of ovarian cell, excluding LTC(4) treatment in LEC. The secretion of PGF(2α) was also increased by LTs, but decreased after LTB(4) treatment of LSC. In GC cultures, both LTs stimulated E2 secretion; in LEC cultures, LTB(4) stimulated whereas LTC(4) inhibited P4 secretion; in LEC cultures, LTC(4) stimulated but LTB(4) inhibited ET-1 secretion. The results show that LTs are produced locally and are involved in PGs production/secretion in all examined cells (LSC, LEC and GC) of bovine ovary. Leukotriene treatment modulate secretion of E2, by GC, P4 by LSC and ET-1 by LEC, which indicates that LTs are involved in regulation of ovarian secretory functions.


Child malnutrition and deprivation--observations in Guatemala and Costa Rica.
Traditional populations consisting of small tribal groups living in close contact with nature may be virtually free from endemic malnutrition owing to the relative absence of infectious diseases. Transition toward modern ways of life and population growth, leading to crowding and underdevelopment, favours endemic malnutrition due to the interaction of malnutrition and infection. Although important features of the traditional culture--breast-feeding, protective child rearing--may remain intact, they are not enough, and such populations exhibit high rates of infectious disease, malnutrition and premature death. In modern industrialized societies, malnutrition often appears related to child abuse and neglect. Organic and metabolic forms are observed but social pathology appears to be the main determinant of most malnutrition observed. Prevention and control of malnutrition requires improvement of the environment and interventions applied in a holistic manner. Emphasis should be given to education and maternal technology, and to promotion of mother-infant interactions, breast-feeding, adequate weaning procedures and detection of factors that may lead to child deprivation and abuse. Improvement is feasible for most developing nations if social forces become conscious of the needed changes, but positive elements of traditinal culture should be preserved.


Function of Nucleus Ventralis Posterior Lateralis Thalami in Acupoint Sensitization Phenomena.
To observe the effect of electroacupuncture (EA) on nucleus ventralis posterior lateralis (VPL) thalami activated by visceral noxious stimulation and to explore the impact of EA on the mechanism of acupoint sensitization under a pathological state of the viscera, EA was applied at bilateral "Zusanli-Shangjuxu" acupoints. The discharge of VPL neurons was response to EA increased after colorectal distension (CRD). The stimulation at "Zusanli-Shangjuxu" acupoints enhanced discharge activity of VPL neurons under CRD-induced visceral pain. The frequency of neuronal discharge was associated with the pressure gradient of CRD which showed that visceral noxious stimulation may intensify the body's functional response to stimulation at acupoints.


A decade of domiciliary non-invasive ventilation in the west of Ireland.
While domiciliary non-invasive ventilation (NIV) was initially used in the treatment of respiratory failure resulting from chest wall deformity, the main indication is now chronic obstructive pulmonary disease (COPD) with recurrent exacerbations associated with type 2 respiratory failure. A longitudinal study of domiciliary NIV provides insights into the evolution of this treatment in the west of Ireland. The cohort of patients receiving new prescriptions for domiciliary NIV from Galway University Hospital from 2000 to 2012 was reviewed using study coordinator chart reviews and telephone follow-ups. In total, 161 patients were identified. Prescriptions for domiciliary NIV increased from 2 in 2000 to 35 in 2012. The most common indication between 2000 and 2006 was obesity hypoventilation syndrome (OHS), changing to COPD between 2007 and 2012. There were significantly higher mortality rates in COPD and neuromuscular disease at 1- and 3-year follow-up compared to OHS and chest wall disease. Patients with chest wall disease had most survival years (7.33 ± 5.51) following initiation of domiciliary NIV when compared to patients with OHS (5.50 ± 3.70) and COPD (3.03 ± 1.89) and patients with neuromuscular disease (2.50 ± 2.01). Domiciliary NIV use increased significantly in the West of Ireland from 2000 to 2012. There has been a shift in prescribing toward COPD. Survival rates for COPD on NIV are relatively short in contrast to patients with OHS and chest wall disease. Improved understanding of the benefits of NIV will allow physicians to better determine appropriate and cost-effective use in the future.


Supracervical hysterectomy.
This guideline reviews the evidence relating to the potential benefits of the vaginal hysterectomy (VH) and supracervical hysterectomy (SCH) versus total abdominal hysterectomy (TAH) with respect to postoperative sexual function, urinary function, and peri- and postoperative complications. Laparoscopic options are not included in this guideline. Women considering hysterectomy for benign disease can be given the option of retaining the cervix or proceeding with a total hysterectomy. The outcomes measured are postoperative sexual function and urinary function, and peri- and postoperative complications. The Cochrane Library, Medline, and Embase were searched for articles published in English from January 1950 to March 2008 specifically comparing VH and SCH with TAH in the prevention of sexual dysfunction, urinary dysfunction, and peri- and postoperative complications. Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies. Additional publications were identified from the bibliographies of these articles. Randomized controlled trials were considered evidence of the highest quality, followed by cohort studies. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. The quality of evidence was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care (Table). 1. Vaginal hysterectomy is generally considered the first choice of surgical approach for most benign indications for hysterectomy, as it is associated with lower rates of morbidity, fewer postoperative complications, and a faster recovery time than abdominal hysterectomy. (I-A). 2. Women contemplating a vaginal, laparoscopic, or abdominal hysterectomy for the management of benign uterine disease should be reassured that hysterectomy is usually associated with improved quality of life, including improved sexual function, whether or not the cervix is removed. (I-B). 3. Supracervical hysterectomy should not be recommended as a superior technique to total abdominal hysterectomy for the prevention of postoperative lower urinary tract symptoms. (I-B). 4. Although supracervical hysterectomy may be associated with less blood loss and a shorter surgical time, these parameters have not been found to be clinically significant, and supracervical hysterectomy should not be recommended as a superior technique to total abdominal hysterectomy for the prevention of peri- and postoperative complications. (I-B). 5. Women considering a supracervical hysterectomy should be counselled that they may continue experiencing cyclic vaginal bleeding following the surgery. (I-B). 6. Women must be advised that they require routine cytological screening following a supracervical hysterectomy. (II-B). 7. Women who require a hysterectomy and who have a current or significant history of abnormal cervical cytological results should be counselled on the advantages of vaginal hysterectomy or total abdominal hysterectomy over supracervical hysterectomy. (I-B).


Analysis of clustered matched-pair data.
Evaluation of the performance of a new diagnostic procedure with respect to a standard procedure arises frequently in practice. The response of interest, often in a dichotomous form, is measured twice, once with each procedure. The two procedures are administered to either two matched individuals, or when practical, to the same individual. A large sample test for matched-pair data is the McNemar test. The main assumption of this test is independent paired responses; however, when more than one outcome from an individual is measured by each procedure, the data are clustered. Examples of such cases can be seen in dental and ophthalmology studies. Variance adjustment methods for the analysis of clustered matched-pair data have been proposed; however, because of unequal cluster sizes, variability of correlation structures within a cluster (within paired responses in a cluster as well as between paired responses in a cluster), and unequal success probabilities among the clusters, the performances of some available methods are not consistent. This research proposes a simple adjustment to the McNemar test for the analysis of clustered matched-pair data. Method of moments is used to calculate a consistent variance estimator. Using Monte Carlo simulation, the size and power of the proposed test are compared to those of two currently available methods. To illustrate practical application, clustered matched-pair data from two clinical studies are analysed.


Provision of cellular blood components to CMV-seronegative patients undergoing allogeneic stem cell transplantation in the UK: survey of UK transplant centres.
To identify current UK practice with regards to provision of blood components for cytomegalovirus (CMV)-seronegative, potential, allogeneic stem cell recipients of seronegative grafts. Infection with CMV remains a major cause of morbidity and mortality after allogeneic stem cell transplantation (aSCT). CMV transmission has been a risk associated with the transfusion of blood components from previously exposed donors, but leucocyte reduction has been demonstrated to minimise this risk. In 2012, the UK Advisory Committee for the Safety of Tissues and Organs (SaBTO) recommended that CMV-unselected components could be safely transfused without increased risk of CMV transmission. We surveyed UK aSCT centres to establish current practice. Fifteen adult and seven paediatric centres (75%) responded; 22·7% continue to provide components from CMV-seronegative donors. Reasons cited include the continued perceived risk of CMV transmission by blood transfusion, its associated morbidity and concerns regarding potential for ambiguous CMV serostatus in seronegative potential transplant recipients due to passive antibody transfer from CMV-seropositive blood donors, leading to erroneous donor/recipient CMV matching at transplant. The survey demonstrated a surprisingly high rate (22.7%) of centres continuing to provide blood components from CMV-seronegative donors despite SaBTO guidance.


Perception of and attitude towards mental illness in Oman.
As conceptions of mental illness are often dictated by prevailing socio-cultural factors and the philosophy of the time, there is little research to substantiate how mental illness is perceived in the Arab world in the light of both traditional and more recent modernization and acculturation processes. To examine whether social factors exert an influence on a person's attitude towards people with mental illness (PWMI) in the rapidly changing country of Oman. This study compares the response elicited from medical students, relatives of psychiatric patients and the general Omani public on the causes of mental illness, attitudes toward PWMI and the care and management of people with mental illness. This study found no relationship between attitudes towards PWMI, and demographic variables such as age, educational level, marital status, sex and personal exposure to people with mental illness. Both medical students and the public rejected a genetic factor as the cause of mental illness; instead they favoured the role of spirits as the aetiological factor for mental illness. There were favourable responses on statements regarding value of life, family life, decision-making ability, and the management and care of mental illness. However, both medical students and the public thought that PWMI tend to have peculiar and stereotypical appearances and the majority preferred that facilities for psychiatric care should be located away from the community. Although the relatives of psychiatric patients were concerned about the welfare of mental patients, their responses varied and were often contingent upon their expectations. The data suggest that neither socio-demographic factors nor previous exposure to PWMI was related to attitudes towards PWMI. Although the attitudes of Omanis toward PWMI appear to fluctuate in complex ways, traditional beliefs on mental illness have yet to be eroded by exposure to a biomedical model of mental illness. This study largely supports the view that the extent of stigma varies according to the cultural and sociological backgrounds of each society.


Effect of calfhood vaccination on transmission of bovine viral diarrhea virus under typical drylot dairy conditions.
To estimate transmission of bovine viral diarrhea virus (BVDV) and crude morbidity and mortality ratios in BVDV-vaccinated and unvaccinated dairy heifer calves managed under typical dairy drylot conditions. Randomized clinical trial. 106 female Holstein calves. Seroconversion rates for BVDV types I and II and proportional morbidity and mortality ratios were compared between calves given a killed BVDV type-I vaccine at 15 days of age and a modified-live BVDV type-I vaccine at 40 to 45 days of age (n = 53) and calves given no BVDV vaccines (53). Sera were collected at 45-day intervals as calves moved from individual hutches to corrals holding increasingly larger numbers of calves. Seroconversion was used as evidence of exposure to BVDV. Crude proportional morbidity (0.16) and mortality (0.17) ratios for control calves did not differ significantly from those of vaccinated calves (0.28 and 0.12, respectively). The proportion of control calves that seroconverted to BVDV type I through 9 months of age (0.629) was significantly higher than that of vaccinated calves that seroconverted, unrelated to vaccination, during the same period (0.536). Estimated overall protective effect of vaccination against BVDV type I through 4 to 9 months of age was 48%. The proportion of control calves that seroconverted to BVDV type II (0.356) was not different from that of vaccinated calves (0.470). Findings suggest that calfhood vaccination may be an appropriate strategy to help reduce short-term transmission of some but not necessarily all strains of BVDV.


Perception of blackness.
We sought to measure the mechanisms underlying the perception of blackness in the following way. A central spot (45') of fixed luminance was surrounded by a dark ring (7.5'), and surrounding all was an annular zone (30') of light. This stimulus was presented in Maxwellian view for 0.5 sec every 3 sec. The radiance of the annulus required to make the central area (spot and ring) appear uniformly black was measured for different wavelengths (440-660 nm) of the annulus. These measurements were made for test spots that were either broadband or of wavelength 480, 500, 580, or 660 nm. In all conditions the measured spectral efficiency of induced blackness matched the inverse of the V lambda function. Using the same stimulus, we have also measured increment-threshold functions. For a fixed luminance of the spot, the radiance of the surrounding annulus required to bring the central spot to threshold was measured. These increment-threshold functions do not match the V lambda or blackness functions. Our results show that induced blackness is inversely related to the luminous efficiency function and that the spectral efficiency of induced blackness is distinct from the increment-threshold function measured under these conditions. Furthermore, blackness appears to be independent of the wavelengths of the inducing annulus as well as of the central spot. Thus these results link induced blackness to the luminance pathway and argue against the involvement of the chromatic pathways in the perception of blackness.


Statin therapy decreases myocardial function as evaluated via strain imaging.
The purpose of this study was to evaluate the effects of statin therapy on myocardial function as measured with echocardiography with tissue Doppler imaging (TDI) and strain imaging (SI) independent of its lipid-lowering effect. Statin use is known to improve outcomes in the primary and secondary prevention of ischemic heart disease, but their use is also associated with myopathy, muscle weakness and in rare cases, rhabdomyolysis. We sought to evaluate whether TDI and SI is able to identify changes in myocardial function associated with statin use. Myocardial function was evaluated in 28 patients via echocardiography with TDI and SI. We identified 12 patients (5 females) without overt cardiovascular disease (including hypertension, smoking, and diabetes) that were on statin therapy and compared their echocardiographic findings with 16 (12 females) age, sex, and cholesterol-profile-matched controls. Tissue Doppler imaging parameters of diastolic (E(')/A(') and E/E(')) and systolic (S') function were measured. Regional systolic function was obtained by SI in 4-chamber, 2-chamber, long axis, and average global views. There was no significant difference in myocardial function as measured by Doppler and minor differences as measured via TDI among the 2 groups. There was significantly better function noted with SI in the control group vs the statin group in the 4-chamber (-19.05% +/- 2.45% vs -16.47% +/- 2.37% P = 0.009), 2-chamber (-20.30% +/- 2.66% vs -17.45% +/- 4.29% P = 0.03), long axis (-17.63% +/- 3.79% vs -13.83% +/- 3.74% P = 0.01), and average global (-19.0% +/- 2.07% vs -15.91% +/- 2.81% P = 0.004) views. Statin therapy is associated with decreased myocardial function as evaluated with SI.


Sympathetic neural adjustments to stress in physically trained and untrained humans.
The purpose of this study was to determine if the state of physical training influences sympathetic neural activation during acute stress in humans. We recorded muscle sympathetic nerve activity (microneurography of the peroneal nerve), arterial blood pressure, and heart rate in 12 highly trained, endurance athletes (25 +/- 1 years, mean +/- SEM) and 12 untrained subjects (27 +/- 1 years) before (supine rest control) and during: 1) lower body negative pressure at -5, -10, -15, and -20 mm Hg (orthostatic stress); 2) isometric handgrip at 30% of maximum (exercise stress); and 3) hand immersion in ice water, that is, the cold pressor test (thermal stress). Body weight was not different in the two groups, but the athletes had a lower body fat content (8.9 +/- 1.3% versus 16.1 +/- 2.0%, p less than 0.05). During supine rest, muscle sympathetic nerve burst frequency (24 +/- 3 versus 24 +/- 2 bursts/min, athletes versus untrained subjects) and burst incidence (36 +/- 3 versus 44 +/- 4 bursts/100 heart beats) and arterial blood pressure were not different in the two groups, but heart rate was lower in the athletes (54 +/- 2 versus 67 +/- 3 beats/min, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)


Sleep and optimism: A longitudinal study of bidirectional causal relationship and its mediating and moderating variables in a Chinese student sample.
While both sleep and optimism have been found to be predictive of well-being, few studies have examined their relationship with each other. Neither do we know much about the mediators and moderators of the relationship. This study investigated (1) the causal relationship between sleep quality and optimism in a college student sample, (2) the role of symptoms of depression, anxiety, and stress as mediators, and (3) how circadian preference might moderate the relationship. Internet survey data were collected from 1,684 full-time university students (67.6% female, mean age = 20.9 years, SD = 2.66) at three time-points, spanning about 19 months. Measures included the Attributional Style Questionnaire, the Pittsburgh Sleep Quality Index, the Composite Scale of Morningness, and the Depression Anxiety Stress Scale-21. Moderate correlations were found among sleep quality, depressive mood, stress symptoms, anxiety symptoms, and optimism. Cross-lagged analyses showed a bidirectional effect between optimism and sleep quality. Moreover, path analyses demonstrated that anxiety and stress symptoms partially mediated the influence of optimism on sleep quality, while depressive mood partially mediated the influence of sleep quality on optimism. In support of our hypothesis, sleep quality affects mood symptoms and optimism differently for different circadian preferences. Poor sleep results in depressive mood and thus pessimism in non-morning persons only. In contrast, the aggregated (direct and indirect) effects of optimism on sleep quality were invariant of circadian preference. Taken together, people who are pessimistic generally have more anxious mood and stress symptoms, which adversely affect sleep while morningness seems to have a specific protective effect countering the potential damage poor sleep has on optimism. In conclusion, optimism and sleep quality were both cause and effect of each other. Depressive mood partially explained the effect of sleep quality on optimism, whereas anxiety and stress symptoms were mechanisms bridging optimism to sleep quality. This was the first study examining the complex relationships among sleep quality, optimism, and mood symptoms altogether longitudinally in a student sample. Implications on prevention and intervention for sleep problems and mood disorders are discussed.